This study is concerned with pharmacokinetics of central nervous system drugs, the relation of pharmacokinetics to pharmacodynamics and the nature of the modifying influence of senescence. Biodisposition of haloperidol was examined in 3 and 33 month-old male Fischer-344 rats. Plasma and regional brain (striatum mesolimbus, frontal cortex and cerebellum) concentrations were measured after extraction, by gas chromatographic assay with nitrogen selective detector. Plasma elimination half-life of haloperidol was longer and plasma and regional brain concentrations were significantly higher at 6 and 9 hrs after bolus intraperitoneal injection in 33 month-old rats. During continuous intraperitoneal administration, plasma and regional brain concentrations of haloperidol were not significantly different between the two age groups. Regional brain concentrations of haloperidol did not correlate with regional dopamine receptor density.